341 results for 2000, Undergraduate

  • Loving our national parks to death

    Mann, Amber (2005)

    Undergraduate thesis
    University of Otago

    iii, 91 leaves :col. ill., plan ; 30 cm. Includes bibliographical references.

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  • Desperate measures : murder, marriage and the media, 1900-1939

    McNair, Alexandra (2003)

    Undergraduate thesis
    University of Otago

    91 leaves :ill. ; 30 cm. Includes bibliographical references. Typescript (photocopy). "1 October, 2003."

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  • Alpine fault pseudotachylytes

    Ritchie, Samuel David (2009)

    Undergraduate thesis
    University of Otago

    xvii, 171 leaves :col. ill., maps30 cm Includes bibliographical references. "October 2009". University of Otago department: Geology

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  • Domestic disquiet? : New Zealand responses to conflict in Malaya/Malaysia 1954-1966

    Sargison, Georgina (2006)

    Undergraduate thesis
    University of Otago

    viii, 89 leaves, [9] leaves of plates :ill., facisms., ports. ; 30 cm. Bibliography: leaves 84-89. Typescript (photocopy).

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  • Vestibular Function in Vestibular Schwannoma

    Tranter-Entwistle, Isaac Brian (2016)

    Undergraduate thesis
    University of Otago

    Abstract Introduction: Traditionally vestibular function has been assessed using caloric irrigations; new methods have failed to reach the same level of accuracy. Vestibular nerve dysfunction occurs with ‘acoustic neuroma’ or ‘vestibular schwannoma. Quantitative testing of hearing by audiometry is much more widely available than quantitative vestibular testing, although consideration of vestibular dysfunction is part of clinical management. Validation of a new method of quantitative vestibular function testing could lead to more widespread integration into clinical practice and affect decision making (i.e. timing of surgery) Methods: A non-blind observational cohort study was undertaken in 31 participants. Study endpoints were either one or two separate participant measures in March/April 2013 the September/October 13. All participants underwent caloric and head impulse testing with video-oculography, while 10 underwent audiometric assessment. Repeat testing was performed for 10 subjects, including additional cognitive. The primary outcome was vestibular function test measures. Results: Video head impulse was strongly correlated with calorics (p=0.01) and showed good sensitivity (80%) and specificity (70%). Dizziness Handicap Inventory showed no correlation with other vestibular function measures. Participants showed reduced cognitive function tested using the CANTAB battery (p=0.01) Conclusion: Video head impulse testing is comparable to caloric testing to assess vestibular function. Vestibular lesions may lead to cognitive deficits. Further research is needed to better understand the role of video head impulse testing in vestibular schwannoma.

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  • Intellectual capital disclosures by Australian companies

    Woodcock, Richard James (2007)

    Undergraduate thesis
    University of Otago

    Australia is shifting towards a knowledge-based economy. Even though there is an increasing emphasis on intellectual capital by Australian firms there is no mandatory intellectual capital disclosure standard. This suggests that what intellectual capital information Australian companies disclose is done voluntarily. This study examines whether this voluntary intellectual capital disclosure is occurring and whether a company’s characteristics influence the level of its intellectual capital disclosure by proposing two research questions. Firstly, what is the extent and content of voluntary intellectual capital disclosures by Australian companies? And secondly, what firm-specific characteristics are determinants of voluntary intellectual capital disclosures by Australian companies? Content analysis is used to gather data on intellectual capital disclosure levels and content of a sample of seventy listed Australian companies. Analysing the descriptive statistics of this data addresses this study’s first research question. In order to attend to the second research question five firm-specific characteristics are examined, industry classification, ownership concentration, leverage, listing age, and auditor type. Five hypotheses propose whether these five independent variables have an association with the level of intellectual capital disclosures or not. To operationalise the level of intellectual capital disclosure, as a dependent variable, the data gathered from the content analysis is utilised to calculate a disclosure index. Correlation and multiple regression analyses are performed to statistically test the five hypotheses. This study found that there is a limited awareness by Australian companies towards intellectual capital disclosures. The levels of intellectual capital disclosures were reasonably low and there was also inconsistency of the level of disclosure among firms. In terms of the content of disclosures, external capital was found to be the most frequently disclosed category of intellectual capital. This finding was consistent with previous intellectual capital disclosure studies in the Australian context. Through statistical testing, this study found that companies that operate in high intellectual capital intensive industries, and companies with a Big Four auditing firm disclose greater levels of intellectual capital information. It was found that a company’s ownership concentration, leverage level, and listing age do not influence its intellectual capital disclosure behaviour. The results of this study extend the scant research in this area of accounting, and they also provide practical implications for Australian accounting standard regulators.

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  • IC3:Information and Communication integration using VCoIP between 3 collaborating parties

    Sun, Jian (2006-10)

    Undergraduate thesis
    University of Otago

    This study develops a new communication and collaboration supported tool – IC3. In particular, this tool is an integration of open source video conference over internet protocol (VCoIP) and virtual network computing (VNC) projects. This integrated system supports both virtual communication and collaborated web information sharing. In addition, it aims to facilitate greater eye contact and seating arrangements. The results from a set of heuristic evaluations show that the IC3 system is an effective communication and collaboration tool, and it does improve users’ eye contact and feeling of sitting around a table.

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  • Genome Architecture and Phenotypic Plasticity: Is the Lethal (2) Essential for Life cluster epigenetically regulated during ovary activation in the honeybee, Apis mellifera?

    Lovegrove, Mackenzie R. (2013)

    Undergraduate thesis
    University of Otago

    Phenotypic plasticity is the ability of an organism to alter its phenotype, without altering its genome, in response to environmental cues. There is mounting evidence it is involved in human development, where it has been implicated in the risk of developing noncommunicable adult diseases. Studying the molecular basis of this in mammals can be difficult, particularly separating out single influences from complex environmental interactions. The honey bee, Apis mellifera, provides a useful model in which to study plasticity because of its well-controlled, easily triggered plastic responses. Queen bees are normally the only reproductively active females within a hive, but workers can activate their ovaries in response to the loss of the queen. During this process, over a third of the genome shows altered gene expression, implying that coordinated gene regulation within a chromatin domain may play a role. We have identified a candidate cluster for investigating this hypothesis, the Lethal (2) Essential for Life (L(2)efl) group. The genes of which are down-regulated as the workers undergo ovary activation. The findings of this study show that the original boundaries of the chromatin domain had been underestimated, and that the CTCF insulator element binding sites which flank the genes of the Lethal(2)efl cluster, LOC100576174 and Gmap, appear to be the boundaries of the coordinated regulation. All of the genes within these sites show co-ordinated regulation, with expression occurring in the terminal filament cells of the ovary in queens, workers and active workers. As ovary activation is a phenotypically plastic response to an environmental cue, it was hypothesised that the mechanisms which underlie it are epigenetic in nature, with previous work identifying the repressive histone mark H3K27me3 as likely playing a role in ovary activation. Potential binding sites for the ecdysteroid-regulated transcription factors BR-C Z1 and Z4 were found for all of the genes within the CTCF binding sites, and none directly outside it (LOC411452 and LOC412824). The proposed model for the coordinated regulation of the genes within the chromatin domain containing the L(2)efl group is through an interaction of both histone modifications and ecdysteroid-regulated transcription factors. This work provides evidence for large scale, coordinated changes in gene expression leading to phenotypic plasticity in response to an environmental influence.

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  • Abduction Strength Deficiency: How Common, How Early and How Amendable?

    Chen, Shumou (2014)

    Undergraduate thesis
    University of Otago

    Gluteus medius strength deficiency has been linked to various injuries of the lower limb (Fairclough et al., 2007, Bullock-Saxton et al., 1993, Powers et al., 2003, Williams and Cohen, 2009). However there is limited information in the literature about the prevalence of this condition among healthy individuals. When observing peoples’ walking patterns, it is common to see excess side to side movement indicative of abduction strength deficiencies. However the conventional dynamometry strength testing generally show normal results despite the person having an abnormal gait pattern and the conventional exercise used to treat this condition is not yet proven to be effective. A recently published study on Australian Rules footballers suggested that hip abduction weakness does occur in healthy people when a previously unpublished test was used. It uncovered the weakness and using the same position as an exercise was capable of correcting it (Osborne et al., 2012). The current study investigated the testing position against conventional testing positions and the exercise against conventional exercises. This study also investigated the possibility of growth related hip abduction strength deficiency in high school aged males. Three studies were used to investigate the new testing position and exercise. An observational study among 101 healthy adults was completed to investigate the prevalence of hip abduction strength deficiency and compare the new hip abduction testing position to conventional hip abduction testing positions. An interventional study was completed to investigate the effects of the new abduction exercise against a conventional abduction exercise and an adduction exercise as controls. This study involved three 1st XV rugby teams with a intervention period of two months. The third study was also an observational study involving 105 high school students. This study investigated the prevalence of abduction strength deficiency in relation to growth among high school aged males. In the study involving healthy adults, it was found that people tested the weakest in the new testing position. When the new hip abduction exercise was compared to conventional hip abduction exercises and an addcution exercise as a control, there were no significant strength improvements. The third study also found no hip abduction strength deifciency realted to growth among high school aged males. The recently published testing position may be a useful tool in uncovering hip abduction strength deficiency but as an exercise it did not produce any significant strength gains. Although a recently published study on Australian Rules Footballers suggested that hip abduction strength deficiency may occur due to growth (Osborne et al., 2012), this study suggested there were no growth related hip abduction strength deficiency.

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  • The Effects of Pharmacological Preconditioning with GYKI-52466 and Domoic Acid on LTP and LTD Induction in the Rat Hippocampus

    Macindoe, Jessica Ellen (2013)

    Undergraduate thesis
    University of Otago

    Many neurodegenerative diseases are associated with severe memory loss and cognitive impairment, highlighting a critical demand for the development of neuroprotectants and nootropics. It has been shown that certain compounds can trigger lasting neuroprotective mechanisms. This phenomenon is called ‘pharmacological preconditioning,’ and it has recently been suggested that preconditioning may also enhance cognitive function. Indeed, preconditioning with GYKI-52466 and domoic acid (DOM) has prophylactic neuroprotective efficacy in vivo and in vitro, and preliminary in vitro results demonstrate their ability to enhance long term synaptic potentiation (LTP) and long term depression (LTD), thus denoting nootropic potential. The aim of the present study was develop an effective in vitro preconditioning strategy using GYKI-52466 or DOM, and clarify their effects on LTP and LTD induction in the rat hippocampus. Hippocampal slices from male Sprague Dawley rats were subject to acute or chronic preconditioning with 6 μM GYKI-52466, or acute preconditioning with 50 nM DOM. Control slices were not preconditioned. Slices subsequently underwent LTP or LTD induction, and electrophysiological techniques were used to assess the response to this. Orthodromic Schaffer collateral-evoked CA1 population spikes and field excitatory postsynaptic potentials (fEPSP) were monitored before and after LTP or LTD induction. Data were expressed as mean percentage change from baseline (± SEM) and group differences compared to controls at a 30 minute time-point post LTP or LTD induction was determined by an unpaired student’s t-test at a confidence level of P<0.05. GYKI-52466 and DOM preconditioning failed to enhance LTP and LTD induction. Both control and preconditioned slices exhibited comparable magnitudes of LTP and LTD for population spike amplitude, area and fEPSP slope, with no significant differences between control and preconditioned slices evident at a 30 minute time-point. These findings suggest that preconditioning with GYKI-52466 and DOM would not confer nootropic potential.

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  • Quality of Diabetic Foot Care in Oman

    Al-Busaidi, Ibrahim Saleh (2014)

    Undergraduate thesis
    University of Otago

    Background Diabetes mellitus is a common and increasingly important chronic disease worldwide. In Oman, the setting of this thesis, the prevalence of diabetes was 12.3% in 2008. Diabetes causes substantial morbidity and mortality, with diabetic foot disease (DFD) being one of the most serious and costly complications of diabetes. Good preventive foot care measures, patient and provider education and adherence to proper foot self-care practices can reduce the risk of developing DFD by up to 85.0%. No published study has investigated diabetic foot care in Oman. Objectives The aim of this study was to explore the quality of diabetic foot care provided by primary and secondary health care professionals in an area of Muscat, Oman. The specific objectives were: 1) To ascertain the level of foot self-care amongst people with diabetes; 2) To determine the level of foot care education for people with diabetes provided by primary and secondary health care professionals; 3) To determine the level of professional foot care services provided to people with diabetes; and 4) To examine the association between foot self-care practices and known risk factors for diabetes-related foot disease (DRFD). Methods The study setting was eight primary health care clinics and one polyclinic in Alseeb, Muscat, Oman. A convenience sample of 350 Omani patients with diabetes (310 from primary health care and 40 from the polyclinic) were invited to participate in the study. A questionnaire developed from two pre-existing questionnaires and pre-tested and translated into Arabic, was administered by author of this thesis and research assistants. The questionnaire included six domains including demographic details, patient-reported DRFD, foot self-care, foot care education, and professional foot care. Data were checked, entered into Excel spreadsheet, and analysed using STATA Statistical Software version 12.0 (2012). Proportions and means were calculated as appropriate for variables of interest. To examine the association between dependent and independent variables, a one-way analysis of variance was used for categorical variables and product-moment correlation test for continuous variables. Ethical approval was obtained from the Medical Research and Ethics Review Committee, Ministry of Health, Oman. Results Of the 350 participants, 62.3% were female and more than half of the patients were illiterate (52.9%). DRFD was found to be common in this population with more than 55.0% of the study population reported having at least one or more sensory peripheral neuropathy symptoms, and almost half (49.1%) complained of one or more peripheral vascular disease symptoms in the last month. In spite of this, patients often did not adopt all recommended behavioural foot care practices. For example, 54.7% did not look at the bottoms of their feet daily, 58.4% reported using moisturising creams or lotions between their toes daily, and 46.0% reported wearing traditional Omani sandals which do not offer protection from injuries. Fewer than half of the participants reported receiving advice or information on recommended foot care practices from their diabetes health care professionals. Professional diabetes foot care services were suboptimal. For example, 20.4% of participants reported never being asked about numbness in their feet and 21.7% reported having been seen by a podiatrist during the previous year. In the final model, a statistically significant association was found between foot self-care scores and level of formal education, diabetes treatment and professional foot care. Conclusions and recommendations Despite the presence of DRFD in this Omani population with diabetes, the overall quality of diabetic foot care was suboptimal. From the patient perspective there is a need for high quality diabetic foot care education to improve patients’ foot care awareness and self-management. Patient education requires good communication skills and an understanding of patients’ education levels, and the influence of cultural, social and religious practices. A multidisciplinary team approach and ongoing foot care education for health care professionals is needed in order to improve their diabetic foot care knowledge and skills. To better understand the context, barriers to regular recommended foot self-care practices needs to be explored further, and the reasons for non-adherence to the Omani diabetes foot care guidelines by health care professionals requires further clarification. Nevertheless, findings from this study will be useful for health care planners and policy makers in Oman and neighbouring countries with similar health systems for improving the overall quality of diabetes foot care.

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  • Isolation and characterization of human dental pulp derived stem cells

    Kang, Isaac (Jinho) (2013)

    Undergraduate thesis
    University of Otago

    Background: Dental caries remains a major public health concern. Dental endodontics (root canal) therapy involves extirpating the dental pulp and replacing with inert materials. For severe tooth decay, it is the only available treatment; however, it fails to restore the biological functions and vitality of the dental tissues and may ultimately leads to tooth loss. To overcome these shortcomings, dental pulp stem cells (DPSCs) are being investigated as a novel prospective approach to regenerate the dental tissue. In this study, we isolated and purified DPSCs and characterized the purified cells. Objectives: The aims of this study were as follows: (i) to rapidly extirpate dental pulp tissues from human third molar teeth under sterile conditions; (ii) to isolate, characterize, and purify a heterogeneous population of DPSCs using mesenchymal stem cell markers; (iii) to determine the ability of DPSCs to differentiate down an odontoblastic lineage. Design: DPSCs were mechanically and chemically isolated from human impacted third molar teeth. Cells were expanded, passaged, and a heterogeneous population of DPSCs isolated using a cloning cylinder. DPSCs were characterized and purified by flow cytometry using the mesenchymal stem cell markers, STRO-1, CD44, and CD146. DPSCs were induced under two different odontogenic conditions comprising different concentrations of beta-glycerophosphate, and dexamethasone. DPSCs were analysed for morphology, proliferation potential, collagen formation, mineralization characteristics, and expression of the dentin-specific markers dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1), using immunohistochemistry. Results: DPSCs were positive for the mesenchymal stem cell markers STRO-1, CD44, and CD146, although two populations of cells showed different levels of STRO-1 expression. Differentiated DPSCs (dDPSCs) demonstrated a significant increase in alkaline phosphatase concentration between days 14 and 21, while a similar increase in collagen deposition, mineralization, and calcification was also observed on day 28. The proliferation rate of dDPSCs decreased with time. Odontoblast characteristics of dDPSCs were observed, with increased expression of the dentin-specific markers DSPP and DMP-1. Conclusions: This investigation demonstrated successful isolation of DPSCs and differentiation of DPSCs down an odontoblastic lineage, indicating that DPSCs represent a promising approval for the regeneration of lost dental tissues.

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  • Epigenetics and Expression of SFRP1 and PPARG and Epigenetic Effects of Glucocorticoids in B-cell Acute Lymphoblastic Leukaemia

    Foster, Timothy John (2014)

    Undergraduate thesis
    University of Otago

    B-cell Acute Lymphoblastic Leukaemia (B-ALL), a cancer of immature B-lymphocytes, is the most common cancer in childhood. This cancer is characterised by widespread abnormalities of DNA methylation, when compared with non-cancerous blood cells. DNA methylation is a chemical modification of the cytosine residues of DNA, and only cytosine residues immediately followed by guanine residues (so called CpG sequences or sites) undergo methylation. Methylation of CpG sites in gene promoter regions leads to non-expression of the methylated gene. DNA methylation abnormalities in cancers (such as B-ALL) have received significant attention over recent years, and have been shown to have significant biological effects in tumour cells, due to abnormal expression of the aberrantly methylated genes. This project aimed to show that the putative tumour suppressor genes, SFRP1 and PPARG, showed increased DNA methylation in B-ALL cells, when compared with normal blood cells and that this was associated with reduced expression of these genes in B-ALL. The methylation of the gene promoters was determined by bisulphite sequencing and gene expression by qRT-PCR. The results showed that PPARG and SFRP1 both show increased methylation in the gene promoter regions of B-ALL cells, when compared with normal blood cells. SFRP1 has previously been shown to show reduced expression in B-ALL and the qRT-PCR results showed that the PPARγ-1 transcript from the PPARG gene showed reduced expression in B-ALL cells, when compared with B-cells from normal blood as well as normal whole blood. Overall, it was concluded, on the basis of these results and others’, that SFRP1 and PPARG show reduced expression compared with normal blood cells, due to promoter methylation in B-ALL. It has also been suggested in the literature that glucocorticoid drugs (analogues to the steroid hormone cortisol) can alter the methylation of CpG sites in individual genes (in non B-ALL cells). This is of interest in the context of B-ALL, as glucocorticoids are well known to be strong anti-leukaemia agents and are used in B-ALL treatment. Glucocorticoids are also known to affect the expression of many genes, an effect that is compatible with changing the DNA methylation of cells. Therefore, this project also aimed to show that the glucocorticoid dexamethasone could induce changes in DNA methylation in many genes within the genomes of B-ALL cells. Multi-gene methylation was measured using the, relatively new, RRBS technique with the NALM-6 human B-ALL cell-line with or without exposure to dexamethasone acting as my model of B-ALL. The results showed a number of methylation changes throughout the genome, with some particularly strong methylation changes observed in the promoter regions of the genes SPINT2, GATA3, IRX5, SOX13, GATM, PDGFA and DOCK10; genes implicated in cancer or in steroid-sensitive metabolism (such as energy metabolism). These results suggest that steroids do indeed alter the DNA methylation of B-ALL cells, which, if these results are replicated, is a novel mode of action of glucocorticoids in B-ALL treatment.

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  • Cranberry Capsules: The efficacy of cranberry capsules in the management of acute radiation cystitis in men with prostate cancer

    Hamilton, Katelin (2014)

    Undergraduate thesis
    University of Otago

    Background: Acute radiation-induced cystitis is a common side effect of radiation therapy (RT) to the pelvis, with up to 40-50% of prostate cancer patients suffering from cystitis to some extent. Acute symptoms can occur within weeks of radiation treatment and include urinary urgency, frequency, dysuria, and hematuria. Currently there is no effective treatment for radiation cystitis. Here, in a double-blinded pilot study, we investigated the effect of standardised cranberry capsules on the extent of radiation-induced cystitis, and how this impacts on quality of life in prostate cancer patients. Methodology: A total of 41 men receiving RT for prostate cancer at the Southern Blood and Cancer Center (SBCC) in Dunedin participated in this trial, which opened in May 2012. The men took one capsule a day during breakfast from their first day of treatment until two weeks after completion of treatment. This took place regardless of which arm they were randomised to. Cranberry capsules contained 72mg of proanthocyanidins (PACs) each and were indistinguishable from placebo capsules. Patients, clinicians and research assistants were blinded to the content of the capsules. Severity of cystitis was assessed using a modified urinary domain of the Expanded Prostate Cancer Index Composite (EPIC) scale. Items included severity of symptoms (pain, blood in urine, leakage, urinary frequency in day and night) use of pads and symptomatic relief (URAL), as well as the effect of these symptoms on daily life. Results: This thesis analysed the results of the first 10 cranberry and 10 control patients who presented with low baseline EPIC scores. The results showed that cranberry capsules seem to decrease certain aspects of radiation cystitis both with regard to physical symptoms and the effect on quality of life. However results in this small cohort did not generally reach statistical significance and limitations of the trial methodology have been recognised. Conclusion: In light of the limitations of this trial and the positive trends in the results, further investigation is warranted. Future research should focus particularly on establishing consistent hydration levels, regulating the use of symptomatic relief and developing improved methods for assessing the level of acute radiation cystitis.

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  • Global sourcing in New Zealand manufacturing firms: A quantitative investigation

    Davidson, Bethany (2003)

    Undergraduate thesis
    University of Otago

    Global sourcing is a resource acquisition strategy that has created much interest in recent years. As firms strive to remain competitive in an increasingly challenging business environment, many have looked for suppliers outside of their home country in order to develop competitive advantages in their domestic markets. Prior research has shown that significant benefits can be gained from the international integration and co-ordination of their purchasing activities. The aim of this dissertation is to investigate the incidence and application of global sourcing in New Zealand manufacturing firms. A review of the literature relating to the philosophy of supply chain management (SCM) provides the foundation for a discussion of global sourcing. The global sourcing literature focuses heavily on foreign countries, particularly the United States of America. This investigation aims to improve the deficiency that exists in this area, by examining global sourcing within a different context. A quantitative research method in the form of a web-based survey was conducted in this investigation. The data that was obtained from the survey was statistically analysed and a number of results were gained. These results were then discussed and reconciled with the literature with the purpose of determining whether they are consistent with what has already been established. Three key findings of this investigation are highlighted. Firstly, the level of global sourcing strategy pursued by New Zealand manufacturing firms is low, which may indicate a limited ability or need to carry out higher, sophisticated levels of global sourcing strategy. Secondly, New Zealand manufacturing firms have been motivated to pursue global sourcing primarily by 'cost reductions / price benefits'. This reflects the extent to which less expensive labour, less restrictive work rules and lower land and facility costs have enticed many to look at global suppliers. Finally, the major barriers that have caused difficulties for New Zealand manufacturing firms in their pursuit of global sourcing have been identified as 'exchange rate fluctuations' and 'longer lead times and lengthened material pipelines'. This reflects the impact that market uncertainties and geographical isolation can have on the ability of firms to successfully pursue global sourcing.

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  • Bone Tissue Engineering: Generation of Autologous Bone from Mesenchymal Stem Cells

    Stace, Edward Thomas (2011)

    Undergraduate thesis
    University of Otago

    Bone tissue engineering is a developing technology with the promise of generating autologous bone grafts from small bone marrow samples. The ability to culture bone tissue from small marrow samples removes many of the problems associated with current autologous bone grafting techniques specifically donor site morbidity, supply and quality bone tissue. Whilst bone tissue engineering is being researched elsewhere, the exciting prospect of bone banking is novel. We see the cryopreservation of cultured bone for use in later life as an intriguing opportunity for people employed in hazardous jobs such as the armed forces and those engaging in potentially traumatic interests like skiing. To begin bone banking research, a successful bone tissue engineering protocol was required. There were three aspects to this work; defining a protocol for isolation of an appropriate cell population, generation of a suitable three dimensional scaffold and design of a perfusion culture system. This thesis examines these three initial aspects. Mesenchymal Stem Cells (MSCs), isolated from rat femoral bone marrow, were expanded and differentiated down the osteoblastic lineage by 28 days culture in a dexamethasone based osteogenic media. Over this osteogenic culture period, cells developed a cuboidal osteoblast-like morphology. Immunohistochemical staining showed these cells increased the expression of the known bone markers; collagen I, osteocalcin, osteopontin, osteonectin and bone sialoprotein. Additionally, osteogenic cultures showed a 200 fold increase in alkaline phosphatase (ALP) concentration. Scanning Electron Microscopy (SEM) showed the deposition of a highly fibrillar matrix surrounding the osteoblast-like cells in osteogenic cultures. Immunohistochemically, this matrix stained positively for collagen I and alizarin red staining showed mineralization of this matrix. Contrastingly, no change in morphology, no extracellular matrix and no increase in ALP concentration were noted in control conditions. For bone tissue culture, a chitosan-hydroxyapatite scaffold was generated through a freeze drying process. Micro Computer Tomography (µCT) and computer analysis showed the mean pore diameter was 228 µm. SEM surface analysis showed the hydroxyapatite distributed evenly within the scaffold. After the scaffold was subjected to degradation and cytotoxicity testing, MSCs were seeded onto cover slips coated in the chitosan-hydroxyapatite scaffold. MSCs were seen to adhere to and proliferate on this scaffold. MSCs were then seeded on to chitosan-hydroxyapatite scaffolds and cultured under perfusion conditions in the designed perfusion culture system. After a 10 day culture period no cells were detected on the scaffold. This is believed to be due to the low initial cell seeding density. This research has shown the successful differentiation of MSCs down the osteoblastic lineage, fabrication of a suitable chitosan-hydroxyapatite material, cell adherence to this scaffold material and development of a perfusion cell culture system. However, further optimisation of the perfusion culture protocol is needed. Successful perfusion culture would then allow experimentation with cryopreserved cultured bone and further investigation of the feasibility of bone banking.

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  • MANUKA HONEY: An Investigation into the Effect of Manuka Honey on Oral Mucositis in Patients Receiving Radiation Therapy to the Head and Neck

    Parsons, Emma Kay (2011)

    Undergraduate thesis
    University of Otago

    Head and neck cancer is the sixth most common type of cancer, with an estimated 650,000 registrations and 350,000 deaths worldwide annually (Parkin et al., 2005). The treatment for these types of cancers is becoming increasingly aggressive with the majority of patients receiving a combination of surgery, radiation therapy and chemotherapy to cure their cancer. Severe oral mucositis is a common side effect of these cytotoxic treatments with 60% of patients receiving radiation therapy and 92% of patients receiving chemoradiation developing it during the course of their treatment (Parulekar et al., 1998; Sonis, 1998; Dodd et al., 2000; Elting et al., 2003). Oral mucositis leads to many secondary complications including severe oral pain, difficulty in eating and swallowing, taste changes, infection, malnutrition and weight loss. Currently, there is no standard form of treatment for oral mucositis with the majority of treatments aimed at palliation of symptoms rather than preventing or treatment oral mucositis itself. The research presented in this thesis investigates the effect of manuka honey on the prevention and treatment of radiation induced oral mucositis in patients receiving radiation therapy and chemoradiation for head and neck cancers at the Palmerston North Oncology Department. The original study was designed as a stage II randomised single blinded trial where patients were randomised into one of two arms. Patients in the control arm were given the standard treatments for oral mucositis in New Zealand including Benzydamine Hydrochloride (HCL), bicarbonate rinses, pain killers and anti-fungals. Patients in the experimental arm were given all standard treatments and were asked to gargle 20mls of undiluted manuka honey three times per day. Patients oral mucositis was scored three times per week, they were weighed once per week and asked to fill out a food and drug diary everyday and a quality of life questionnaire once every fortnight during treatment. Due to poor patient compliance with the undiluted honey this trial was downgraded to a phase I pilot trial investigating the best way to administer manuka honey to treat oral mucositis. This thesis specifically reports the results for twelve patients recruited to this trial between March 2009 and December 2009. Due to the early downgrading of this trial from a randomised phase II trial to a pilot trial the effects of pure undiluted manuka honey on radiation induced oral mucositis could not be assessed. There was no statistically significant difference in the severity of oral mucositis reported between those taking diluted manuka honey and those using standard forms of treatment only. Patients taking diluted manuka honey appeared to have slightly less weight loss than those receiving standard treatments alone however this did not reach statistical significance. All patients, irrespective of whether they were taking honey or not, reported a severe decrease in quality of life throughout the course of their radiation therapy. There were large issues with patient compliance in this trial. Even when the honey had been diluted significantly patients complained the honey tasted too sweet, made them feel nauseous and stung their oral mucosa. Due to these issues with compliance, it was not deemed ethical to continue with the current trial unless the honey is given to patients is a way which is tolerated better.

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  • Effect of Delayed Treatment with Mesenchymal Stem Cells on Neonatal Hypoxic/Ischemic Brain Injury: A Behavioral and Stereological Study

    Alwakeel, Amr J. (2011)

    Undergraduate thesis
    University of Otago

    Hypoxia/ischemia is a major cause of acute neonatal brain injury and may lead to the development of neurological disabilities, mainly cerebral palsy. Hypoxic/ischemic (H/I) injury occurs as a result of decreased oxygen level in the brain and/or blood and reduced perfusion of the brain tissue. One of the main sites involved in neonatal H/I brain injury is the striatum. In children, injury to the striatum results in the muscular abnormalities of cerebral palsy. Medium-spiny neurons constitute the major neuronal population of the striatum in both primates and rodents. Hence, the rescue or restoration of the medium-spiny neuron population is a viable aim in treating neonatal H/I injury. Current evidence has shown hypothermia, a neuroprotective strategy, to be effective in treating H/I injury. However, hypothermia and other neuroprotective strategies can only be administered within 2 – 6 hours post-injury. The aim of this study was to investigate the therapeutic potential of a seven-day delay in treatment with mesenchymal stem cells (MSCs), a neurorestorative strategy, following hypoxia/ischemia in the neonatal rat. Furthermore, the effect of a subcutaneous injection of a high-dose (HD, 7.5 x 10^5 – 1 x 10^6) and of a low-dose (LD, 8.5 x 10^4 – 1.2 x 10^5) of MSCs was investigated. This was the first study to assess the efficacy of the subcutaneous route of delivery in mesenchymal stem cell (MSC) therapy following neonatal H/I injury. On postnatal day (PN) 7, male pups were exposed to H/I injury. After a seven-day delay (i.e. PN 14), pups were weight-matched in pairs or triplets and randomly assigned to either a diluent injection of Dulbecco's phosphate-buffered saline (DPBS) or a MSC injection. In the LD MSC experiment, five pups were administered the diluent while six pups received a LD MSC injection. In the HD MSC experiment, seven pups were administered the diluent while nine pups received a HD MSC injection. The therapeutic effect was assessed using behavioral testing, and stereological analysis of the absolute total number of striatal medium-spiny neurons. On PN 20, the functional outcome was assessed using the negative geotaxis, cylinder, elevated body swing and foot-fault tests. Each pup was sacrificed on PN 21 and their brain was dissected from the cranium. Injured hemispheres were subsequently embedded in Technovit, serially sectioned and stained. Sections were stereologically analyzed using the Cavalieri method and optical disector method to estimate the absolute number of striatal medium-spiny neurons between diluent- and MSC-receiving pups. To our knowledge, this was the first study that used unbiased modern stereological methods to quantify the absolute number of medium-spiny neurons in the striatum following MSC therapy in neonatal hypoxia/ischemia. A sub-aim of this study was to determine the efficacy of the negative geotaxis test in the study of neonatal H/I injury before the administration of any treatments. As such, pups were tested on the negative geotaxis apparatus on PN 12 and PN 14, prior to MSC and diluent injections on the afternoon of PN 14. The findings of this study showed that a seven-day delay in MSC treatment did not have a statistically significant improvement on the functional outcome following H/I injury. However, a positive trend was observed in the cylinder test in pups receiving MSCs. MSC administration resulted in a higher preference of using the contralateral injured limb over the ipsilateral uninjured limb when compared to the diluent-administered pups. This positive trend was more profound in the HD MSC group compared to the LD MSC pups. The stereological findings showed that delayed MSC therapy was effective in attenuating the loss in striatal medium-spiny neurons compared to diluent-receiving pups. This difference was found to be statistically significant. The HD MSCs were more effective than the LD MSCs and restored the number of striatal medium-spiny neurons to normal levels. The subcutaneous route was also shown to be an effective route in delivering MSCs. Finally, results from the negative geotaxis test showed that this test may not be an effective assessment in evaluating the functional outcome following neonatal H/I brain injury. In conclusion, the findings of this study suggest that delayed MSC therapy can be an effective tool in treating neonatal H/I brain injury. These findings may offer hope to children who have missed the critical period of 2 – 6 hours post-injury, which is limited to neuroprotective interventions.

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  • Measuring the Physical Activity of Children aged 3 to 7 years

    Ku, Hsi-Yu (2011)

    Undergraduate thesis
    University of Otago

    Introduction : Obesity has become epidemic throughout the world and is affecting both adults and children. New Zealand children have a high prevalence of being overweight, with estimates varying between 20% and 30%. Sedentary behaviour (SB) is an important mediator of successful prevention of developing overweight in children. However a reliable objective method for measuring SB is still lacking. Effective prevention of excessive weight gain could flow from having an objective device with a clear definition of SB. Accelerometers are motion sensing devices which have been used to study physical activity (PA) with promising validity in children. As one of the steps in establishing the utility of accelerometers in measuring SB, we aimed to assess the reliability and validity of the Actical accelerometer for its use in 3-7 year old children and to propose an appropriate cut-off that defines SB. Methods : Children (N=50) aged 3-7 year old were recruited in Dunedin, New Zealand, to participate in the study. The study was carried out at the participants’ preschool centre or school. The children were asked to wear the Actical accelerometer around their waist and to perform numerous selected activities of varying levels of intensity. At the same time, participants were video recorded for observational analysis to provide the criterion measure of PA. Activities performed during free play sessions at participants’ preschool centre or school were also measured. Reliability of the Actical accelerometers was assessed daily throughout the data collection phase using a custom-made motion generator. Validity of the accelerometer was assessed by comparing with activity levels measured by direct observation using the Children’s Activity Rating Score (CARS). The appropriate cut-off to define SB was determined by plotting the receiver operating characteristic curve, and the cut-off derived was then cross-validated by comparing with levels of SB measured by using the CARS. Results : Height, weight and BMI distributions of the children assessed (N=49) were comparable with published data on New Zealand children. Reliability tests during the data collection phase revealed high intra-instrument and inter-instrument reliabilities (r p-intra & r p-inter =1.0). Repeated measurements by the same accelerometer gave small differences (<0.05) and were categorised into four groups: inactivity (Sleep), sedentary level movement (Draw, Play Doh, Puzzle, Read, TV), light level activities (Toy Car), activities of higher intensities (Nintendo Wii and Free Play). Using the receiver operating characteristic curve (area under the curve: 0.843), a cut-off of 40 counts/15s was identified (sensitivity: 88.44% and specificity: 64.63%). For the children assessed by the CARS (N=9), correlation between Actical counts and CARS score was moderate (r p =0.56). The mean difference of percentage of time in sedentary activity judged by accelerometry compared to direct observation using CARS was 8.4%. There were no significant differences in the percentages of sedentary activity between accelerometer data versus CARS (p=0.055). Conclusions : Overall, the study has proposed a cut-off for SB of 40 counts/15s. Despite having obtained moderate correlation with the criterion measure, it appears that this cut-off tends to slightly under predict levels of SB and accurate prediction of SB is limited by sub-optimal inter-instrument agreement. Performance of the Actical could be improved if accurate calibration were possible outside the manufacturer. Utility of the cut-off could be further assessed by conducting a cross-validation of the cut-off with a larger sized sample. Outcome : The results of this study could be used in ongoing studies that use the Actical accelerometers to measure activity in children aged 3 to 7 years.

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  • Prolactin Regulation of Kisspeptin Neurons

    Crampton, Jessica Rose (2011)

    Undergraduate thesis
    University of Otago

    It is well established in both humans and rodents that the state of hyperprolactinaemia leads to reduced reproductive capacity, as a consequence of suppressed luteinising hormone secretion. Return of reproductive function can be achieved by physiological gonadotropin-releasing hormone (GnRH) administration in humans. In rodents, there is no decrease in pituitary GnRH responsiveness in the presence of elevated prolactin. These findings indicate that prolactin, an anterior pituitary hormone capable of direct action in the central nervous system, is affecting hypothalamic GnRH secretion, rather than pituitary gonadotropin secretion. However, as prolactin receptors are only expressed on a small minority of GnRH neurons, a direct suppressive action by prolactin on these neurons is unlikely. Hence, an indirect mechanism utilising neurons afferent to GnRH neurons may be in place. The neuropeptide kisspeptin has recently been discovered to be a key afferent regulator of GnRH secretion. Prolactin receptors are present on the majority of kisspeptin neurons, leading to the hypothesis of this thesis; that prolactin inhibits kisspeptin neurons, providing an indirect pathway through which prolactin alters GnRH output. To investigate this hypothesis, several experiments were carried out. Firstly, double-label immunohistochemistry, staining for pSTAT5 (an intracellular signal transducer of prolactin signalling) and kisspeptin, was performed throughout the AVPV/PeN and arcuate nuclei of the rat hypothalamus. Colocalisation of pSTAT5 nuclear-staining within kisspeptin neurons was evident in ovine prolactin (oPRL)-treated animals, indicating that the prolactin receptors expressed by kisspeptin neurons are functional in vivo. Secondly, Kiss1 mRNA expression in a lactational model of hyperprolactinaemia was analysed by qPCR. There was a significant suppression of Kiss1 mRNA expression in each nucleus during lactation compared to diestrous levels. This was not reversed by prolactin removal (by bromocriptine-treatment), suggesting a suckling-induced suppression not mediated solely by prolactin. A third treatment group, where pups were removed and oPRL was administered, however, suggested the presence of an additional suppressive effect of prolactin in the arcuate nucleus. Finally, in order to investigate the effects of hyperprolactinaemia without the confounding factors of a lactation, a nonlactational model of chronic hyperprolactinaemia was developed. This trial involved ovariectomy with low level oestradiol replacement, and oPRL administration every 8 hours for 48 hours. Serum oPRL concentration, profiled by serial blood sampling through indwelling jugular cannulae, was found to peak 1 -3 h post-injection (approximately 80 ng/ml) and drop to 0 ng/ml by 6 h post-injection. This oPRL-treatment did not suppress LH concentrations compared to vehicle-treated controls, and thus in this regard, the model was unsuccessful. Nevertheless, the hypothalamic tissue obtained was analysed by qPCR to investigate whether Kiss1 mRNA expression was altered by oPRL-treatment. No significant changes were detected in the AVPV/PeN, whilst in the arcuate, there was a significant four-fold increase in Kiss1 mRNA expression in vehicle-treated, ovariectomised rats. This increase was significantly dampened by approximately half, in oPRL-treated ovariectomised rats. Each of these experiments provide evidence in support of the hypothesis; indicating that prolactin does regulate kisspeptin neurons. This finding could hold important implications for further investigations into the use of kisspeptin as treatment of hyperprolactinaemic infertility, a condition that hinders many patients.

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